A Study of MLN9708 in Japanese Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM)

NCT04272775 | Terminated Phase 1 Results

• 3 other identifiers: TB-MC010034JapicCTI-121822U1111-1243-1737
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics (PK) of ixazomib alone or in combination with lenalidomide and dexamethasone (Rd), and antitumor activity of ixazomib in participants with RRMM.

Conditions

Relapsed and/or Refractory Multiple Myeloma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (7)

• Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

  DLT:Any following adverse events (AEs) possibly related to ixazomib assessed by Common Terminology Criteria for AEs (CTCAE) version 4.03; Grade 4 neutropenia/thrombocytopenia lasting \>7 consecutive days; Grade 3/greater neutropenia with fever/infections; Grade 3/greater thrombocytopenia with clinically significant bleeding; platelet count less than (\<)10,000 per cubic meter(/mm\^3); Grade 2 peripheral neuropathy with pain/Grade 3 or greater peripheral neuropathy; Grade 3/greater nonhematologic toxicities with exceptions of arthralgia/myalgia, fatigue lasting \<7 days manageable nausea/emesis with antiemetic prophylaxis, diarrhea that is controlled with supportive care; treatment delay of \>14 days at start of Cycle 2 due to failure of hematologic/nonhematologic recovery; Other Grade 2/greater ixazomib related nonhematologic toxicities required permanent discontinuation of ixazomib;Inability to receive at least 80% of planned lenalidomide doses due to the AEs related to ixazomib.

  From Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle length is equal to [=] 28 days)

• Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)

  Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

• Number of Participants With Grade 3 or Higher TEAE Related to Body Weight

  Body weight abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).

  Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

• Number of Participants With Grade 3 or Higher TEAE Related to Vital Signs

  Vital signs were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).

  Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

• Number of Participants With Grade 3 or Higher TEAE Related to 12-lead Electrocardiograms (ECGs)

  12-lead ECGs were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).

  Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

• Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities

  Laboratory tests abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).

  Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

• Cmax: Maximum Observed Plasma Concentration for Ixazomib

  Days 1 and 15 of Cycle 1: pre-dose and at multiple time points (15, 30, 60, and 90 minutes and 2, 4, 8, 24, 48, 96, and 168 hours) post-dose (Cycle length=28 days)

Secondary Outcomes (1)

• Number of Participants Who Achieved Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR)

  Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

Study Arms (4)

Cohort 1: Ixazomib 4.0 mg

EXPERIMENTAL

Ixazomib 4.0 milligram (mg), capsules, orally, once, on Days 1, 8, and 15 in 28-day treatment cycle for up to Cycle 87.

Drug: Ixazomib

Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone

EXPERIMENTAL

Ixazomib 4.0 mg, capsules, orally, once, on Days 1, 8, and 15 in 28-day treatment cycle along with lenalidomide 25 milligram per day (mg/day), capsules, orally, once, from Days 1 to 21 and dexamethasone 40 mg/day, tablets, orally, once, on Days 1, 8, 15, and 22 in 28-day treatment cycle for up to Cycle 62.

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Cohort 3: Ixazomib 5.5 mg

EXPERIMENTAL

Ixazomib 5.5 mg, capsules, orally, once, on Days 1, 8, and 15 in 28-day treatment cycle for up to Cycle 87.

Drug: Ixazomib

Cohort 4: Ixazomib 5.5 mg + Lenalidomide and Dexamethasone

EXPERIMENTAL

Ixazomib 5.5 mg, capsules, orally, once, on Days 1, 8, and 15 in 28-day treatment cycle along with lenalidomide 25 mg/day, capsules, orally, once, from Days 1 to 21 and dexamethasone 40 mg/day, tablets, orally, once, on Days 1, 8, 15, and 22 in 28-day treatment cycle for up to Cycle 87.

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib capsules.

Also known as: MLN9708

Cohort 1: Ixazomib 4.0 mg; Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone; Cohort 3: Ixazomib 5.5 mg; Cohort 4: Ixazomib 5.5 mg + Lenalidomide and Dexamethasone

Lenalidomide DRUG

Lenalidomide capsules.

Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone; Cohort 4: Ixazomib 5.5 mg + Lenalidomide and Dexamethasone

Dexamethasone DRUG

Dexamethasone tablets.

Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone; Cohort 4: Ixazomib 5.5 mg + Lenalidomide and Dexamethasone

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Japanese participants with multiple myeloma according to diagnostic criteria.
• Previously treated with 2 or more regimens including all the following drugs; bortezomib, thalidomide or lenalidomide, corticosteroids.
• Who have relapsed following the previous therapy or failed to continue the treatment due to their intolerability to the last treatment regimen for myeloma.
• Measurable disease defined by at least one of the following 3 measurements; Serum M-protein: greater than or equal to (\>=) 1 gram per deciliter (g/dL) (\>= 10 gram per liter \[g/L\]), Urine M-protein: \>= 200 mg/24 hours, Serum free light chain (FLC) assay: involved FLC level \>= 10 milligram per deciliter (mg/dL) (\>= 100 milligram per liter \[mg/L\]), provided that the serum FLC ratio is abnormal.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• years or older at giving their informed consent.
• Must be able to stay in the hospital for Cycle 1 treatment.
• Must meet the following laboratory criteria at screening; Absolute neutrophil count (ANC): \>=1,000 per cubic millimeter (/mm\^3), Platelet count: \>=75,000/mm\^3, Total bilirubin: \<=1.5\* the upper limit of normal range (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): less than or equal to (\<=) 3\* ULN, Creatinine clearance: calculated by using Cockcroft-Gault formula; MLN9708 monotherapy cohort: \>=30 milliliter per minute (mL/min); MLN9708 with Rd cohort: \>=60 mL/min.
• Recovered (\<= Grade 1) from the toxicities of the prior treatments. ANC \>=1,000/mm\^3.
• Life expectancy of at least 3 months, in the judgment of the investigator.
• Conforming to proper management guidelines of lenalidomide (MLN9708 with Rd cohort only).

You may not qualify if:

• With plasmacytoma only.
• With plasma cell leukemia.
• With central nervous system invasion.
• Radiotherapy within 14 days before enrollment.
• Other anti-tumor drug administration within 21 days before enrollment.
• Other investigational products administration within 21 days before enrollment (60 days from the last dose for carfilzomib).
• Antibody treatment within 42 days before enrollment.
• Systemic treatment with potent cytochrome P450 (CYP) isozyme 1A2 inhibitors (fluvoxamine, enoxacin), potent CYP3A inhibitors (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole), or potent CYP3A inducers (rifampin, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of foods containing Ginkgo biloba extract, St. John's Wort, or grapefruit within 14 days before enrollment.
• Treatment with corticosteroids greater than (\>) 10 mg of prednisolone per day. Inhaled and topical steroids are permitted.
• Peripheral neuropathy \>=Grade 2.
• Diarrhea \>= Grade 2.
• Major surgery requiring general anesthesia within 14 days before enrollment.
• Infection requiring systemic antibiotic treatment or other serious infections within 14 days before enrollment.
• Evidence of concurrent uncontrolled cardiovascular conditions including hypertension, cardiac arrhythmias, New York Heart Association (NYHA) Class III or worse congestive heart failure, angina, myocardial infarction, or cerebral infarction within 6 months before enrollment.
• Corrected QT interval (QTc) \> 470 milliseconds on a 12-lead ECG obtained during the screening period.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Interventions

ixazomib; Lenalidomide; Dexamethasone

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: June 5, 2012
• Primary Completion: February 15, 2019
• Study Completion: February 15, 2019
• Last Updated: March 17, 2020
• Results First Posted: February 28, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share